Profiling Carbohydrate Metabolism in Liver and Hepatocellular Carcinoma with [13C]‐Glycerate Probes. Issue 4 (23rd September 2021)

• Record Type: Journal Article
• Authors: Chen, Jun; LaGue, Evan; Li, Junjie; Yang, Chendong; Hackett, Edward P.; Mendoza, Manuel; Alger, Jeffry R.; DeBerardinis, Ralph J.; Corbin, Ian R.; Billingsley, Kelvin L.; Park, Jae Mo
• Is Part Of: Analysis & Sensing. Volume 1:Issue 4(2021)
• Page Start: 196
• Page End: 202
• Publication Date: 2021-09-23
• Subjects: glycerate -- hepatocellular carcinoma -- hyperpolarized 13C -- metabolism -- NMR spectroscopy; Chemistry, Analytic -- Periodicals; Analytical biochemistry -- Periodicals; 543
• DOI: 10.1002/anse.202100034
• Languages: English
• ISSNs: 2629-2742

Abstract

Abstract: The interplay between glycolysis and gluconeogenesis is central to carbohydrate metabolism. Here, we describe novel methods to assess carbohydrate metabolism using [ 13 C]‐probes derived from glycerate, a molecule whose metabolic fate in mammals remains underexplored. Isotope‐based studies were conducted via NMR and mass spectrometry analyses of freeze‐clamped liver tissue extracts after [2, 3‐ 13 C2 ]glycerate infusion. The ex vivo investigations were correlated with in vivo measurements using hyperpolarized [1‐ 13 C]glycerate. Application of [ 13 C]glycerate to N‐nitrosodiethylamine (DEN)‐treated rats provided further assessments of intermediary carbohydrate metabolism in hepatocellular carcinoma. This method afforded direct analyses of control versus DEN tissues, and altered ratios of 13 C metabolic products as well as unique glycolysis intermediates were observed in the DEN liver/tumor. Isotopomer studies showed increased glycerate uptake and altered carbohydrate metabolism in the DEN rats. Abstract : The feasibility for 13 C‐labeled glycerates to assess carbohydrate metabolism in the liver was investigated. As compared to wild‐type, N‐nitrosodiethylamine‐treated rats produced (1) higher phosphoenolpyruvate and pyruvate metabolic signals in vivo from hyperpolarized (HP) [1‐ 13 C]glycerate and (2) increased fractional enrichment of glucose and lactate in 13 C NMR of freeze‐clamped tissue extracts, collected after [2, 3‐ 13 C2 ]glycerate infusion.